DOI:10.22034/APJCP.2017.18.7.1765 Simaroubaceae, Quassinoids, Polyphenols REVIEW An Exploration of Phytochemicals from Simaroubaceae Biba Vikas1, B S Akhil2, S R Suja1, K Sujathan2* Abstract Natural products such as plants, animals and minerals have been the basis of treatment of human diseases. Herbal remedies have been used for the treatment of many ailments. Many compounds have been derived from the plant species mentioned in the ancient texts of Indian system of medicine for the treatment of a number of ailments. The R and D thrust in the pharmaceutical sector is focused on development of new drugs, innovative/indigenous processes for known drugs and development of plant based drugs through investigation of leads from the traditional systems of medicine. The family Simaroubaceae is grouped in the order Rutales, is known to have a diverse range of secondary metabolites. Plants from this family are used as medicine to cure cancer and many other diseases. Isolation of diverse chemical compounds from Simaroubaceae on its stem bark, root bark and leaves have been reported. In this review, we are analysing with the chemical constituents of family Simaroubaceae. Keywords: Simaroubaceae- Quassinoids- Polyphenols Asian Pac J Cancer Prev, 18 (7), 1765-1767 Introduction as ailanthinone, glaucarubinone and holacanthone, are considered the plant’s main therapeutic constituents and The Simaroubacea family includes 32 genera and are the ones documented to be antiprotozoal, anti-amebic, more than 170 species of trees and brushes of pantropical antimalarial and even toxic to cancer and leukemic cells distribution.It is characterised by its contents of bitter (www.rain-tree.com/simarouba.html). components, mostly responsible for its pharmaceutical Quassinoids in simarouba family consist of triterpene properties (Fernando et al., 1995, Muhammad et al., 2004). degradation products, derived from the euphol/ tirucalol The main distribution hot spots are located at tropical areas series, highly oxygenated and structurally complex. of America, extending to Africa, Madagascar and regions Regarding the basic structure, they can be structurally of Australia bathed by Pacific.This family is characterised classified into five groups: C-18 (1), C-19 (2), C-20 (3), by the presence of Quassinoids and secondary metabolites C-22 (4) and C-25 (5a, b), though some do not fit into any responsible for the biological activities. given configuration, such as (+)-polyandrol, eurylactones Simarouba is a medium-sized tree that grows up to A and B, ailanquassins A and B, 6-dehydroxylongilactone 20m high, with a trunk of 50-80cm indiameter. It produces and others. Most of the isolated quassinoids have a twenty bright green leaves of 20-50cm length, small white flowers carbon skeleton (Curcino et al., 2006). and small red fruits. It is indigenous to the Amazon The chemical compound Quassia has been used for rainforest and other tropical areas in Mexico, Cuba, malaria in the Amazon region. It has been used topically Haiti, Jamaica, and Central America. The Simaroubaceae for measles and orally or rectally for intestinal parasites, family has been the subject of many studies regarding its diarrhea, and fever (Schulz et al., 1998). The first isolated chemical constitution and numerous compounds were and identified quassinoids were quassin and neoquassin isolated and their structure were elucidated, among these from Quassia amara by Nuclear Magnetic Resonance quassinoids, alkaloids, triterpenes, steroids, coumarins, (NMR) (Clark et al., 1937).Two hundred quassinoids were anthraquinones, and flavonoids and other metabolites currently isolated and identified (Curcino et al., 2007). were present. (Barbosa et al., 2011).Quassinoids can be Thirty nine quassinoids were isolated from nine considered as a taxonomic marker of the Simaroubaceae species of the genus Simaba (Barbosa et al., 2011). There family since it is the most abundant group of natural were reports that ninety one terpenoids were found in substances and their synthesis almost exclusive (Saraiva eight species of the genus Ailanthus, which has been et al., 2006, Almeida et al., 2011). predominantly included quassinoids (Kundu et al., 2004). Quassinoids are the main active group of chemicals A secondary metabolite is a natural product, but a in Simarouba which belongs to the triterpene chemical natural product isn’t necessarily a secondary metabolite family. Several Quassinoids found in Simarouba, such (Bently et al., 1999). Secondary metabolites are 1Jawaharlal Nehru Tropical Botanic Garden and Research, 2Regional Cancer Centre, Trivandrum, Kerala, India. *For Correspondence: [email protected] Asian Pacific Journal of Cancer Prevention, Vol 18 1765 Biba VIkas et al classified depending ontheir structural scaffold. These been identified. The wide spread distribution of flavonoids, classes include among others polyketides (PKs), non their variety and their relatively low toxicity compared ribosomal peptides (NRPs), terpenoids, alkaloids or to other active plant compounds (for instance alkaloids) hybrid metabolites of the different classes. The function mean that many animals, including humans, ingest of secondary metabolites in their hosts has not yet been significant quantities in their diet. Preliminary research exploited to its fullest; however, they seem to have indicates that flavonoids may modify allergens, viruses, several functions including defense, communication, and and carcinogens, and so may be biological “response signaling (Calvo et al., 2002, Fox et al., 2008, Kempken modifiers”. In vitro studies show that flavonoids also et al., 2010, Rohlfs et al., 2011). have anti-allergic, anti-inflammatory, anti-microbial, Although there are notable exceptions (e.g., pal anti-cancer, anti diarrheal and antiviral activities (Spencer toxin, autotoxin), most secondarymetabolites have et al., 2008,Yamamoto et al., 2001,Cushine et al., 2011, relative molecular masses less than 1500 Da. The De Sousa et al., 2007, Schuier et al., 2005), Gonzalez et range of chemicalstructures is breathtaking from al., 1990). simple aliphatic acids (e.g., itaconic acid, C5H6O4) Medicinal plants produce natural products with a large to complexstructures such as alkaloids and toxins diversity of chemical structures, which might prove to be (e.g., palytoxin, C129H223N3O54). This wide range suitable for specific medicinal applications. ofchemical types has made secondary metabolites a major Most of these secondary metabolites show biological topic for study by organic chemists (Bently et al., 1999). activities in pharmaceutically relevant bioassay systems Among the alkaloids isolated from the different genera and thus represent potential lead structures, which could of the Simaroubaceae family, the canthines constitute be optimized toyield effective therapeutic and bioactive a class of β-carboline alkaloids. Canthin-6-ones have agents. been reported to have a large array of activities, such as antiviral, cytotoxic, antiparasitic, antibacterial, high Acknowledgements pro-inflammatory cytokines reducer, among others (Showalter et al., 2013). The authors are gratefully acknowledged to Kerala Twenty triterpenes have been reported in six different State Council for Science, Technology and Environment species of the genus Simarouba (Barbosa et al., 2011). Trivandrum, Kerala, India. There were reports on ninety one terpenoids, which includes quassinoids also (kundu et al., 2004). This class References of secondary metabolites has been largely reported in the literature for numerous genera of Simaroubaceae, Almeida VC, Filho R, Niero BK, et al (2011). Pharmacological like Quassia, Brucea, Picramnia, Castela, Simarouba mechanisms underlying the anti-ulcer activity of methanol and Ailanthus. (kundu et al., 2004). Eight steroids were extract and canthin-6-one of Simabaferruginea A. St-Hil.in isolated from four species of the genus Simaba and their animal models. J Ethnopharmacol, 134, 630-6. Barbosa R, Braz-Filho I (2011). Vieira Chemical constituents structure was elucidated (Barbosa et al., 2011). The of plants from the genus Simaba (Simaroubaceae). Chem isolation of twenty seven steroids from four species of Biodivers, 8, 2163–78. Ailanthus was performed (Kundu et al., 2004). Bentley R (1999). Secondary metabolite biosynthesis: the first Polyphenols, anthraquinones, coumarins, flavonoids, century. Crit Rev Biotech, 19, 1-40. lignans, limonoids, quinines, fatty acids, phenylpropanoids Bhattacharjee SG, Gupta P, Bhattacharya A, et al (2008). Quassin and vitamins have been reported for the different species alters the immunological patterns of murine macrophages of the Simaroubaceae family, although many species have through generation of nitric oxide to exert antileishmanial not been chemically studied yet (Iasmine et al., 2014).The activity. J Antimicrob Chemother, 63, 317-24. vast range of biological activities of the different species of Calvo AM, Wilson RA, Bok JW, et al (2002). Relationship between secondary metabolism and fungal development. Simaroubaceae are given, mainly, due to the quassinoids, Microbiol Mol Biol Rev, 66, 447-59. for which were attributed antitumor, antimalarial, antiviral, Clark EP, Quassin I (1937). The preparation and purification of anorectic, insecticide, amebicide, antiparasitic and quassin and neoquassin, with information concerning their herbicide activities (Bhattacharjee et al., 2008). Coumarin molecular formula. J Am Chem Soc, 59, 927–31. is a fragrant compound in the benzopyrone chemical class Curcino V,